Integrins are expressed on a cell membrane, and constitute a single-transmembrane heterodimeric adhesion molecule. It has been known to have 24 kinds of integrins including 18 types of a chain and 8 types of 6 chain. By binding to its ligand, the recognized integrin transmits various signals to the inside of a cell, and regulates a variety of cellular biological phenomena such as cell morphogenesis, proliferation, and migration of leukocytes at the sites of inflammation.
In addition, the integrin α8 chain forms a heterodimer with the β1 chain to be the integrin α8β1. This integrin recognizes RGD stites in extracellular matrix proteins such as fibronectin, vitronectin, tenascin, and osteopontin. The integrin α8 chain is expressed on mesangial cells in a kidney, vascular smooth muscle cells, fibroblasts, or the like. It has been reported in an experiment using knockout mice that the integrin α8 chain is among the most critical integrins during kidney morphogenesis (Non-Patent Document 1). Also, a correlation with a disease is reported, including that the integrin α8 chain is expressed in re-stenotic artery in rats after vascular injury or in lungs of mice with pulmonary fibrosis (Non-Patent Document 2). Detailed physiological functions of this integrin remain unresolved.
Meanwhile, recently, research and development on an antibody medicine and an antibody diagnostic agent has been progressing. Monoclonal antibodies against integrins have been researched on applications to a therapeutic or diagnostic agent for a disease involving the integrins. For example, Natalizumab, a blocking monoclonal antibody which binds to integrin α4β1, having a multiple sclerosis indication (Non-Patent Document 3) has been listed on the market. It has been reported that Vedolizumab exerts a therapeutic effect on inflammatory bowel disease.
As to an anti-integrin α8β1 antibody (hereinafter, may be referred to as an “integrin α8β1-binding antibody”), an antibody which can be used to detect the integrin by Western blotting and an antibody which can be used to detect the integrin by flow cytometry analysis have been described in Non-Patent Document 4.
Patent Document 1 discloses an Fc variant of an antibody which binds to integrin αVβ3. In addition, an embodiment of Patent Document 1 includes integrin α8β1 as a candidate for an integrin binding to the Fc variant.
Patent Document 2 discloses a recombinant human immunoglobulin having an antigen-binding region containing a particular amino acid sequence. Also, the Claims of Patent Document 2 includes integrin α8β1 as an antigen candidate.